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Biomedical subjects

L M Ruilope

Publications and source records attributed to L M Ruilope.

At least 55 records · Page 3Linked to original sources
PubMed2000

Renal implications of the renin-angiotensin-aldosterone system blockade in heart failure.

The renin-angiotensin-aldosterone system actively participates in the derangement of renal function since the early stages of heart failure (HF). A diminished capacity to excrete sodium secondary to increased proximal tubular re-absorption and loss of the renal functional reserve are the two most relevant initial alterations of renal function in which angiotensin II has been proven to act directly. Meanwhile, the octapeptide contributes to maintain glomerular filtration rate (GFR) within normal limits through efferent arteriole vasoconstriction. Administration of angiotensin converting enzyme inhibitors (ACEi) or angiotensin receptor antagonists (ARA) may thus be accompanied by a functional fall in that parameter. Advanced age, higher initial serum creatinine, history of hypertension, diabetes and atrial fibrillation predict the onset of GFR impairment associated with blockade of the renin-angiotensin system. Concomitant administration of betablockers may help to protect renal function, and preliminary data indicate that the combination of ACEi and ARA is not accompanied by a higher renal risk. The good prognostic effects of aldosterone antagonists in HF does not seem to be related to intrarenal effects of these compounds with the exception of preventing potassium loss and hypokalemia. The systematic therapeutic use of drug(s) provided with beneficial renal effects, to treat arterial hypertension or myocardial ischemia, may contribute to delay of, or prevent the development of HF.

Angiotensin Receptor Antagonists↗
PubMed2000

Do we effectively lower blood pressure?

Blood pressure control is needed in order to attain a normalization of the increased cardiovascular risk present in the hypertensive population. However, we are far from obtaining the most effective control of blood pressure. A more aggressive attitude, in particular in high-risk patients, is required, together with an adequate selection of antihypertensive pharmacological therapies. In this sense combined therapy has to be more widely used in patients presenting with the characteristics detailed in the newly published mega-trials like the Hypertension Optimal Treatment study. An adequate selection of the components of combination could also be of interest through a better protective capacity mediated by blood pressure-independent effects.

Antihypertensive Agents↗
PubMed2000

Influence of diabetes and type of hypertension on response to antihypertensive treatment.

The aim of our investigation was to determine whether the presence of additional risk factors or type of hypertension (diastolic or isolated systolic) influences blood pressure (BP) response to treatment. The International Nifedipine GITS Study: Intervention as a Goal in Hypertension Treatment (INSIGHT) study is a double-blinded outcome comparison of calcium channel blockade with diuretics in high-risk patients aged 55 to 80 years. Dynamic randomization between nifedipine once daily and hydrochlorothiazide/amiloride was performed to ensure that approximately equal numbers of patients in the 2 groups had each of the major cardiovascular risk factors. Patients with isolated systolic hypertension were also separately randomized. Atenolol or enalapril was the mandatory second-line drug. In 5669 patients who completed the 18-week titration, BP fell from 172+/-15/99+/-9 mm Hg (mean+/-SD) while receiving placebo to 139+/-12/82+/-7 mm Hg. Twenty-six percent of patients required 2 drugs, and 4% required 3 drugs. Patients with diabetes were the most resistant to treatment, requiring second and third drugs 40% and 100% more frequently than patients without diabetes and achieving marginally the highest final BP, for any risk group, of 141+/-13/82+/-8 mm Hg. Age, smoking, gender, hypercholesterolemia, left ventricular hypertrophy, and existing atherosclerosis had little (<1 mm Hg) or no influence on BP at the end of titration, but all except smoking slightly reduced the initial response of either systolic or diastolic BP. Patients with isolated systolic hypertension were slightly more responsive than average to treatment. Our findings suggest that in patients at high absolute risk of cardiovascular complications from hypertension, the risk factors themselves do not prevent the recommended BP targets from being achieved.

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PubMed2000

New clinical investigations with selective angiotensin II receptor blocker therapy in diabetes and renal disease.

Halting the reduction in glomerular filtration rate (GFR) is the primary aim of any treatment of patients presenting with progressive chronic renal failure, a very common corollary to diabetes. To improve GFR, the high blood pressure (BP) and proteinuria often seen in these patients must both be controlled. These symptoms lead not only to progressive loss of renal function, but also to an increase in cardiovascular risk. Use of angiotensin-converting enzyme (ACE) inhibitors in these patients has been reported to control BP and reduce protein excretion and cardiovascular risk. Complete blockade of angiotensin II (Ang II) action with the highly selective Ang II receptor blocker (ARB) valsartan, both as monotherapy and in combination with ACE inhibitors, is well-tolerated and efficacious in patients with renal failure. Unlike ACE inhibition, ARB treatment leads to no initial reduction in GFR, thus valsartan may be a better agent for the control of BP, with greater renal protection.

Albuminuria↗
PubMed2000

Safety of the combination of valsartan and benazepril in patients with chronic renal disease. European Group for the Investigation of Valsartan in Chronic Renal Disease.

OBJECTIVE: Several experimental and clinical studies indicate that the renin system may play a pivotal role in progressing renal disease. The combination of an angiotensin-converting enzyme inhibitor and an angiotensin receptor blocker could provide a higher degree of blockade of the renin-angiotensin system than either agent alone. Such enhanced suppression might be of benefit for patients exhibiting a progressive decline in renal function because of chronic renal disease. METHODS: A pilot multinational, multicentre, randomized, active-controlled, parallel group open-label study has been conducted in a group of patients with progressive chronic renal failure (creatinine clearance 20-45 ml/min) either with or without proteinuria and hypertension. The primary aim of the study was to investigate the safety and tolerability of the combination of valsartan and benazepril. Patients were randomly assigned to one of three groups: group 1 received valsartan 160 mg once daily (n = 22); group 2 received valsartan 80 mg once daily plus benazepril 5 or 10 mg once daily (n = 42); group 3 received valsartan 160 mg once daily plus benazepril 5 or 10 mg once daily (n = 44). The study lasted for 5 weeks, and in groups 2 and 3 benazepril was added on top of valsartan after the first week of therapy with the angiotensin receptor blocker. RESULTS: Serum creatinine increased in all three groups (mean change within a group: 11 micromol/l in group 1, P= 0.045; 9 micromol/l in group 2, P= 0.030; 15 micromol/l in group 3, P= 0.0006). Serum potassium also increased in all three groups of patients (mean change within a group: 0.28 mmol/l in group 1, P= 0.28; 0.48 mmol/l in group 2, P= 0.0008; 0.36 mmol/l in group 3, P= 0.02). After 5 weeks of treatment, the largest decrease in blood pressure was observed in group 3 (the mean change from baseline in seated diastolic blood pressure (SDBP) and seated systolic blood pressure (SSBP), respectively, were: -2.0 and -11.5 mmHg in group 1; -7.6 and -15.4 mmHg in group 2; -12.6 and -21.6 mmHg in group 3). In addition, both combination treatments resulted in the reduction of proteinuria. The total number of patients with adverse experiences were 10 (45.5%), 14 (33.3%) and 11 (25%) in groups 1,2 and 3, respectively. In six patients (5.6%) therapy was discontinued as a result of adverse experiences. Only one patient in each of the combined therapy groups withdrew from the study because of hyperkalaemia and no patients were forced to withdraw because of an increase in serum creatinine, acute renal failure or hospitalization. CONCLUSIONS: These results indicate that short-term combination of an angiotensin-converting enzyme inhibitor and an angiotensin receptor blocker is safe and well tolerated in patients with moderate chronic renal failure.

Aged↗
PubMed2000

Treatment of hypertension in the very old.

The objective of this study was to compare the long-term efficacy and safety of 6 months' treatment with barnidipine and hydrochlorothiazide (HCTZ) as monotherapy in patients aged > or = 75 years with mild to moderate essential hypertension. This was a randomised, double-blind, dose-titration study performed at 62 centres in 8 countries. A total of 397 patients were enrolled. Following a 4 week single-blind placebo runin, 315 patients with a sitting diastolic blood pressure (SiDBP) of 95-115 mmHg and a systolic blood pressure of 150-200 mmHg were randomised to receive barnidipine 10 mg (n = 159) or HCTZ 12.5 mg (n = 155) once daily. In patients who had not responded (SiDBP > 90 mmHg) after 6 weeks of double-blind treatment, the dose was titrated upwards to barnidipine 20 mg or HCTZ 25 mg. After 18 weeks, those who did not respond to the higher dose had enalapril (up to 10 mg once daily) added to their regimen. Statistically equivalent reductions in SiDBP were achieved with barnidipine and HCTZ monotherapy. At week 18 of double-blind treatment on monotherapy, 84% of patients in both groups were responders. The addition of enalapril in non-responders produced a further reduction in blood pressure. Both drugs were well tolerated. The incidence of drug-related adverse events was greater in the barnidipine than HCTZ-treated group but they were consistent with vasodilation and were categorised as mild to moderate. In conclusion, barnidipine and HCTZ are well tolerated and have equivalent long-term antihypertensive efficacy in older hypertensive patients. For patients whose blood pressure is inadequately controlled on monotherapy, combination therapy with enalapril is effective.

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PubMed1999

[Spanish contribution to the HOT (Hypertension Optimal Treatment) study. Final results. Spanish Investigators in the HOT study].

BACKGROUND: The HOT study is a multicenter international trial which included 19,193 patients and whose goal was to assess the optimal target diastolic blood pressure to achieve by antihypertensive treatment. PATIENTS AND METHODS: Patients were recruited in 26 countries. Spain contributed with 806 patients (4.3%) who were randomized to achieve three target DBP: < or = 90; < or = 85; and < or = 80 mmHg, respectively. Baseline characteristics, blood pressure achieved by treatment and cardiovascular events are described and compared with the whole HOT sample. RESULTS: Mean age of the 806 Spanish patients was 61.9 +/- 7.3 years (range 50-80), 58.2% being women. About 55.6% were on pharmacological antihypertensive treatment and not controlled at inclusion. There were significant differences in gender, higher number of females (p > 0.001), less prevalence of tobacco consumption (p = 0.014), and a fewer number of patients with angina (p > 0.001) and myocardial infarction (p > 0.04) between the Spanish sample and the whole HOT population. The percentage of patients reaching the randomized target blood pressure was 76.5% at the end of the study. Average systolic and diastolic blood pressure reduction was 28.5 mmHg, and 23 mmHg respectively. The average number of drugs required per patient was 1.7 (57.6% needed two or more antihypertensive drugs) and the number of cardiovascular events in the Spanish population was 40 (4.96%), a similar incidence to the observed (687 events) in the whole study population (3.65%; p = 0.06). CONCLUSION: Strategies of intensive treatment with current antihypertensive drugs are capable to achieve blood pressure control in the great majority of Spanish essential hypertensive patients without significant side effects, thus being responsible for a very low rate of cardiovascular events in these patients.

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PubMed1999

Induction of microalbuminuria by l-arginine infusion in healthy individuals: an insight into the mechanisms of proteinuria.

Despite evidence from individuals with diabetes mellitus or reduced renal mass, the actual relationship between protein- or amino acid-induced changes in renal function and urinary albumin excretion (UAE) is largely unknown in subjects without renal disease. In humans, infusions of l-arginine have been used recently in vascular and renal pathophysiological studies. The present study was undertaken to analyze the mechanisms involved in a particular effect; namely, the behavior of UAE during amino acid loading. A prospective interventional protocol was performed on 10 healthy adults by means of an intravenous infusion of l-arginine. The main results show that l-arginine induced a significant increase in UAE from 13.1 +/- 3.8 before to 53.3 +/- 11.1 microgram/min after the infusion (P < 0.005). This increment was simultaneous to an increase in glomerular filtration rate (GFR) and renal plasma flow (RPF). Furthermore, l-arginine markedly increased the urinary excretion of beta2-microglobulin. UAE correlated significantly with GFR (r = 0. 738; P = 0.014) and RPF (r = 0.942; P < 0.0001), but not with urinary beta2-microglobulin (r = 0.05; P = not significant). Furthermore, marked differences (P = 0.001) were found between the percentage of increase in UAE (306.8% +/- 163.2%) with respect to either albumin filtered load (FLAlb; 57.9% +/- 16.3%) and beta2-microglobulin excretion (1,088.5% +/- 424.6%). No changes were found in vehicle-infused individuals. In conclusion, the present study shows, in controlled conditions, that l-arginine infusion induces a relevant increase in UAE in healthy individuals that significantly exceeds that expected from the increase in GFR alone. The intense and simultaneous increment in beta2-microglobulin excretion strongly suggests that the effect of l-arginine on UAE is, in a relevant part, mediated through a blockade in the tubular protein reabsorption pathways. However, the profound differences observed in the changes induced by l-arginine on UAE and beta2-microglobulin excretion and the differences in the correlation of UAE and beta2-microglobulin with respect to GFR suggest that substantial diversity exists in the mechanisms by which l-arginine affects the renal management of albumin and beta2-microglobulin. These findings are relevant for understanding the renal response to l-arginine and protein/amino acid loads.

Adult↗
PubMed1999

Differential effects of losartan and doxazosin on vascular function in senescent spontaneously hypertensive rats.

We evaluated the effects of treatment for 12 weeks with 10 mg/kg/day of either losartan or doxazosin on vascular function in senescent spontaneous hypertensive rats (SHR). Both doxazosin and losartan reduced blood pressure, although the former was more effective. In contrast, both drugs reduced relative aortic weight and increased plasma nitrates to a similar extent. Losartan, but not doxazosin, increased the magnitude of the response to acetylcholine (10(-9) to 10(-5) mol/L). Both treatments increased relaxations to sodium nitroprusside (10(-10) to 10(-6) mol/L). These data show that losartan may possess advantages over doxazosin in improving vascular function in senescent SHR. This report emphasizes the importance of angiotensin II in vascular function alterations induced by aging in SHR.

Acetylcholine↗
PubMed1999

Hyperkalemia in patients infected with the human immunodeficiency virus: involvement of a systemic mechanism.

BACKGROUND: The appearance of hyperkalemia has been described in human immunodeficiency virus (HIV)-positive patients treated with drugs with amiloride-like properties. Recent in vitro data suggest that individuals infected with HIV have alterations in transcellular K+ transport. METHODS: With the objective of examining the presence of alterations in transmembrane K+ equilibrium in HIV-positive patients, we designed a prospective, interventional study involving 10 HIV-positive individuals and 10 healthy controls, all with normal renal function. An infusion of L-arginine (6%, intravenously, in four 30-min periods at 50, 100, 200, and 300 ml/hr) was administered, and plasma and urine electrolytes, creatinine, pH and osmolality, total and fractional sodium and potassium excretion, transtubular potassium gradient, plasma insulin, renin, aldosterone, and cortisol were measured. RESULTS: A primary disturbance consisting of a significant rise in plasma [K+] induced by L-arginine was detected in only the HIV patients but not in the controls (P < 0.001 between groups). A K+ redistribution origin of the hyperkalemia was supported by its rapid development (within 60 min) and the lack of significant differences between HIV-positive individuals and controls in the amount of K+ excreted in the urine. The fact that the HIV-positive individuals had an inhibited aldosterone response to the increase in plasma K+ suggested a putative mechanism for the deranged K+ response. CONCLUSIONS: These results reveal that HIV-infected individuals have a significant abnormality in systemic K+ equilibrium. This abnormality, which leads to the development of hyperkalemia after the L-arginine challenge, may be related, in part, to a failure in the aldosterone response to hyperkalemia. These results provide a new basis for understanding the pathogenesis of hyperkalemia in HIV individuals, and demonstrate that the risk of HIV-associated hyperkalemia exists even in the absence of amiloride-mimicking drugs or overt hyporeninemic hypoaldosteronism.

Adult↗
PubMed1999

Effects of antihypertensive therapy on factors mediating endothelium-dependent relaxation in rats treated chronically with L-NAME.

OBJECTIVES: To evaluate the relative participation of endothelium-derived factors mediating relaxation in response to acetylcholine in isolated mesenteric vascular beds from rats treated chronically with N(G)-nitro-L-arginine methylester (L-NAME); and to compare the consequences of prolonged treatment with either an angiotensin converting enzyme inhibitor or a calcium channel blocker on the components of acetylcholine-induced relaxation in this vascular preparation. MATERIALS AND METHODS: Male Sprague- Dawley rats were treated for 8 weeks with L-NAME (40 mg/kg per day), quinapril (10 mg/kg per day), diltiazem (100 mg/kg per day), L-NAME + quinapril and L-NAME + diltiazem. Systolic blood pressure was estimated by a tail-cuff plethysmograph. Relaxing responses to acetylcholine (10(-12) to 10(-8) mol) in mesenteric vascular beds precontracted with phenylephrine (10(-5) mol/l) were studied in the presence and absence of L-NAME (10(-5) mol/l), L-NAME + indomethacin (10(-5) mol/l) or L-NAME + indomethacin + potassium chloride (6 x 10(-5) mol/l). The area under the dose- response curve was used to calculate the approximate participation of nitric oxide, prostaglandins or endothelium-derived hyperpolarizing factor in the acetylcholine-induced relaxation. RESULTS: Chronic administration of L-NAME increased blood pressure levels and vascular responsiveness to phenylephrine. Treatments with either quinapril or diltiazem reduced blood pressure levels and attenuated the increased response to phenylephrine. Relaxing responses to acetylcholine were similar in all groups, independently of the treatment received. The calculated participation of endothelium-derived hyperpolarizing factor in the acetylcholine-induced relaxation was higher than that of nitric oxide and prostaglandins in all groups, but was higher in L-NAME-treated than in untreated rats. In contrast, the participation of both nitric oxide and prostaglandins was higher in control than in L-NAME-treated rats. Quinapril increased the participation of prostaglandins in L-NAME-treated rats. Diltiazem increased the participation of nitric oxide in L-NAME-treated rats. CONCLUSIONS: The administration of L-NAME in Sprague-Dawley rats increased the production of endothelium-derived hyperpolarizing factor as a compensatory mechanism to maintain acetylcholine-induced relaxation. Antihypertensive therapy with either quinapril or diltiazem produced a selective redistribution of the endothelial factors mediating acetylcholine-induced relaxation.

Acetylcholine↗
PubMed1999

Uric acid as a cardiovascular risk factor in arterial hypertension.

BACKGROUND: Increased serum urate concentrations is a frequent finding in patients with hypertension. Since hyperuricaemia is associated with obesity, renal disease, hyperlipidaemia, and atherosclerosis the question as to whether serum urate is a cardiovascular risk factor per se has remained elusive. In considering the relationship between uric acid and hypertension three aspects should be answered: (a) the significance of hyperuricaemia; (b) the pathophysiological mechanism of the association; and (c) whether hyperuricaemia is deleterious. SIGNIFICANCE OF HYPERURICAEMIA: Several arguments favour the concept that increased serum urate in hypertensive patients most likely reflects renal vascular involvement. PATHOPHYSIOLOGICAL MECHANISM: Hyperuricaemia is accompanied by a relatively diminished uric acid excretion rate in hypertensive patients. Selective insulin resistance and hyperinsulinism estimulates the tubular sodium-hydrogen exchanger and facilitates the active reabsorption of urate. IS HYPERURICAEMIA DELETERIOUS?: In addition to the renal (urolithiasis) and articular disturbances that hyperuricaemia may cause, vascular damage due to arterial hypertension may limit the availability of oxygen for ATP synthesis. Tissue hypoxia determines increased adenine nucleotide degradation which ends in uric acid overproduction. The formation of uric acid is accompanied by an enhanced synthesis of reactive oxygen species which play a significant role in tissue damage. The hypothesis that hyperuricaemia indicates hypertensive vascular damage is plausible and if unequivocally demonstrated may contribute to delineate evidence-based therapeutic strategies for hypertensive-hyperuricaemic patients.

Humans↗
PubMed1999

Prospective comparison of therapeutical attitudes in hypertensive type 2 diabetic patients uncontrolled on monotherapy. A randomized trial: the EDICTA study.

OBJECTIVE: To compare the anti-hypertensive effect of combination therapy versus a single drug regimen schedule (dose-titration or switching to a different drug class) in type 2 diabetic hypertensive patients with inadequate blood pressure (BP) control on monotherapy. DESIGN: Prospective, randomized, open-fashion, parallel study of two therapeutic strategies during an 8-week period. SETTING: Primary care centers in Spain. PARTICIPANTS: A total of 898 men and women with type 2 diabetes mellitus and hypertension, receiving antihypertensive treatment with one single drug and whose BP was > 140 and/or 90 mmHg. INTERVENTION: Patients were randomized to a fixed combination therapy (verapamil 180 mg plus trandolapril 2 mg; Knoll AG, Ludwigshafen, Germany) or continued on a single drug regimen, either increasing the dose of the current drug or switching to a different drug class. MAIN OUTCOME MEASURE: Absolute BP reduction in the two groups of treatment, and the percentage of normalized patients (< 140/90 mmHg) in each group. RESULTS: The diastolic BP (DBP) decrease (5.6 mmHg) was significantly greater in patients treated with combination therapy, compared to patients on monotherapy (2.9 mmHg). The decrease in systolic BP (SBP) was not significantly different (11.1 versus 10.0 mmHg). In addition, a significantly higher number of patients treated with combination therapy (82% versus 74%) reached diastolic BP normalization (< 90 mmHg). CONCLUSIONS: In type 2 hypertensive patients with uncontrolled BP despite anti-hypertensive monotherapy, the change to combination therapy was more effective in attaining DBP control than any monotherapy schedule (either increasing the dose or switching to another different drug class).

Aged↗